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  • 1
    In: Trials, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2040523-6
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  • 2
    In: JMIR Mental Health, JMIR Publications Inc., Vol. 8, No. 10 ( 2021-10-7), p. e29963-
    Abstract: Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. Objective In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. Methods The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper–Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. Results By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps 〈 .05), had more preexisting mental health disorders and medical conditions, and were younger than 65 years (all Ps 〈 .001). Conclusions Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics.
    Type of Medium: Online Resource
    ISSN: 2368-7959
    Language: English
    Publisher: JMIR Publications Inc.
    Publication Date: 2021
    detail.hit.zdb_id: 2798262-2
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  • 3
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-6-21)
    Abstract: Pediatric patients with sickle cell disease (SCD) experience a range of medical complications that result in significant morbidity and mortality. Recent advances in prophylactic and curative treatment approaches have highlighted the need for sensitive and clinically-meaningful trial endpoints. The detrimental effects of cognitive and psychological difficulties on social and economic mobility are well described. Although numerous reviews have assessed cognitive outcomes in other rare genetic disorders, SCD has not received the same focus. This review describes the cognitive (i.e., executive function and processing speed) and psychological domains (i.e., depression and anxiety) that are consistently associated with SCD pathology and, therefore, may be of particular interest as clinical trial endpoints. We then discuss corresponding well-validated and reliable cognitive tests and patient-reported outcomes (PROs) that may be appropriate for clinical trials given their robust psychometric properties, ease of administration, and previous use in the SCD population. Further, we provide a discussion of potential pitfalls and considerations to guide endpoint selection. In line with the move toward patient-centered medicine, we identify specific tests (e.g., NIH Toolbox Cognition Module, Wechsler Cancellation Test) and psychological PROs (e.g., PROMIS depression and anxiety scales) that are sensitive to SCD morbidity and have the potential to capture changes that are clinically meaningful in the context of patients' day to day lives. In particularly vulnerable cognitive domains, such as executive function, we highlight the advantages of composite over single-test scores within the context of trials. We also identify general (i.e., practice effects, disease heterogeneity) and SCD-specific considerations (i.e., genotype, treatment course, and disease course, including degree of neurologic, pain, and sleep morbidity) for trial measures. Executive function composites hold particular promise as trial endpoints that are clinically meaningful, amenable to change, relatively easy to collect, and can be incorporated into the routine care of patients with SCD in various settings and countries.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 4
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-6-29)
    Abstract: Research in sickle cell anemia (SCA) has used, with limited race-matched control data, binary categorization of patients according to the presence or absence of silent cerebral infarction (SCI). SCI have primarily been identified using low-resolution MRI, with radiological definitions varying in lesion length and the requirement for abnormality on both fluid attenuated inversion recovery (FLAIR) and T1-weighted images. We aimed to assess the effect of published SCI definitions on global, regional, and lobar lesion metrics and their value in predicting cognition. One hundred and six patients with SCA and 48 controls aged 8–30 years underwent 3T MRI with a high-resolution FLAIR sequence and Wechsler cognitive assessment. Prevalence, number, and volume of lesions were calculated using a semi-automated pipeline for SCI defined as: (1) Liberal: any length (L-SCI); (2) Traditional: & gt;3 mm in greatest dimension (T-SCI); (3) Restrictive; & gt;3 mm in greatest dimension with a corresponding T1-weighted hypo-intensity (R-SCI). Globally, as hypothesized, there were large effects of SCI definition on lesion metrics in patients and controls, with prevalence varying from 24–42% in patients, and 4–23% in controls. However, contrary to hypotheses, there was no effect of any global metric on cognition. Regionally, there was a consistent distribution of SCI in frontal and parietal deep and juxta-cortical regions across definitions and metrics in patients, but no consistent distribution in controls. Effects of regional SCI metrics on cognitive performance were of small magnitude; some were paradoxical. These findings expose the challenges associated with the widespread use of SCI presence as a biomarker of white-matter injury and cognitive dysfunction in cross-sectional high-resolution MRI studies in patients with SCA. The findings indicate that with high-resolution MRI: (1) radiological definitions have a large effect on resulting lesion groups, numbers, and volumes; (2) there is a non-negligible prevalence of lesions in young healthy controls; and (3) at the group-level, there is no cross-sectional association between global lesion metrics and general cognitive impairment irrespective of lesion definition and metric. With high-resolution multi-modal MRI, the dichotomy of presence or absence of SCI does not appear to be a sensitive biomarker for the detection of functionally significant pathology; the search for appropriate endpoints for clinical treatment trials should continue.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 5
    In: Brain Sciences, MDPI AG, Vol. 10, No. 12 ( 2020-12-14), p. 981-
    Abstract: Young individuals with sickle cell anaemia (SCA) experience sleep disturbances and often experience daytime tiredness, which in turn may impact on their daytime functioning and academic attainment, but there are few longitudinal data. Methods: Data on sleep habits and behaviour were taken on the same day as an in-hospital polysomnography. This study assesses the developmental sleep profiles of children and young adults aged 4–23 years old with SCA. We examined retrospective polysomnography (PSG) and questionnaire data. Results: A total of 256 children with a median age of 10.67 years (130 male) were recruited and 179 returned for PSG 1.80–6.72 years later. Later bedtimes and a decrease in total sleep time (TST) were observed. Sleep disturbances, e.g., parasomnias and night waking, were highest in preschool children and young adults at their first visit. Participants with lower sleep quality, more movement during the night and increased night waking experienced daytime sleepiness, potentially an indicator of lower daytime functioning. Factors influencing sleep quantity included age, hydroxyurea prescription, mean overnight oxygen saturation, sleep onset latency, periodic limb movement, socioeconomic status and night waking. Conclusion: Sleep serves an important role for daytime functioning in SCA; hence, quantitative (i.e., PSG for clinical symptoms, e.g., sleep-disordered breathing, nocturnal limb movement) and qualitative (i.e., questionnaires for habitual sleep behaviour) assessments of sleep should be mutually considered to guide interventions.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Physiology Vol. 13 ( 2022-8-29)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-8-29)
    Abstract: In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Y v ) to improve neurological risk prediction. T 2 -relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Y v in patients with sickle cell anemia (SCA). However, prior studies comparing Y v in patients with SCA relative to healthy controls have reported opposing results depending on whether the calibration model, developed to convert blood T 2 to Y v , is based on healthy human hemoglobin (HbA), bovine hemoglobin (HbBV) or sickle hemoglobin (HbS). MRI Quantitative Susceptibility Mapping (QSM) is an alternative technique that may hold promise for estimating Y v in SCA as blood magnetic susceptibility is linearly dependent upon Y v , and no significant difference has been found between the magnetic susceptibility of HbA and HbS. Therefore, the aim of this study was to compare estimates of Y v using QSM and TRUST with five published calibration models in healthy controls and patients with SCA. 17 patients with SCA and 13 healthy controls underwent MRI. Susceptibility maps were calculated from a multi-parametric mapping acquisition and Y v was calculated from the mean susceptibility in a region of interest in the superior sagittal sinus. TRUST estimates of T 2, within a similar but much smaller region, were converted to Y v using five different calibration models. Correlation and Bland-Altman analyses were performed to compare estimates of Y v between TRUST and QSM methods. For each method, t-tests were also used to explore group-wise differences between patients with SCA and healthy controls. In healthy controls, significant correlations were observed between QSM and TRUST measures of Y v, while in SCA, there were no such correlations. The magnitude and direction of group-wise differences in Y v varied with method. The TRUST-HbBV and QSM methods suggested decreased Y v in SCA relative to healthy controls, while the TRUST-HbS ( p & lt; 0.01) and TRUST-HbA models suggested increased Y v in SCA as in previous studies. Further validation of all MRI measures of Y v , relative to ground truth measures such as O 15 PET and jugular vein catheterization, is required in SCA before QSM or TRUST methods can be considered for neurological risk prediction.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564217-0
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1945-1945
    Abstract: Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, often isolated hemoglobin concentration (Hb) values obtained from a single time-point closest to data collection. Studies of pediatric patients with phenylketonuria and Type I diabetes have demonstrated that longitudinal change and variability in phenylalanine and glucose, respectively, are better indicators of neurological and cognitive outcomes than a single value alone. Our study aimed to be the first study of pediatric patients with SCA to examine the extent to which indices of Hb control (e.g., lifetime average and variability), collected routinely in this patient group, may provide additional prognostic information. Methods: Data were collected from pediatric patients (aged 4-18 years at enrolment) with and without SCA enrolled on the Sleep Asthma Cohort-III (SAC-III) follow-up study. SAC is a mixed retrospective-prospective study assessing the impact of nocturnal oxygen desaturation on SCA complications. The present investigation assessed participants (see Figure 1 for complete participant demographics) who underwent cognitive evaluation using Wechsler scales measuring domains of IQ, processing speed (i.e., processing speed index [PSI] and Cancellation subtest), and executive function (working memory index [WMI] ). Participant demographics and appropriate medical data and history (i.e., hydroxyurea therapy, silent infarction) were obtained via questionnaires and analysis of medical records. Hb (d/L) measures assessed included average lifetime values (i.e., mean and median), variability over the lifetime (i.e., standard deviation), and the single value obtained closest to data collection. Results: Correlation analyses indicated a strong positive relationship between the mean and median Hb values along with large positive associations between the average and contemporaneous values. Small non-significant correlations were demonstrated between variability and average Hb values (see Figure 1). Initial hierarchical linear regression analyses demonstrated that neither hydroxyurea use nor silent infarct (SCI) status were predictors of any cognitive outcomes or Hb values, so they were not included in any further analyses. Separate regression analyses for each cognitive outcome found that mean lifetime Hb values was the only significant predictor of IQ (p = .04, η 2 = .13) and the Cancellation subtest (p = .005, η 2 = .22). Mean lifetime Hb values approached significance for PSI (p = .09, η 2 = .08), but was not a predictor for WMI (p = .33, η 2 = .03). Conclusion: Our study demonstrated that despite strong correlations between Hb obtained closest to testing and average lifetime values (i.e., rs = .64 and .69), only lifetime Hb predicted cognitive outcomes, particularly processing speed scores from the Cancellation subtest. Variability was not strongly related to other indices of Hb control and did not predict any cognitive outcomes. These results mirror those obtained from other pediatric populations indicating that static, one time values may not best represent clinical manifestations of chronic illness, and the choice of Hb value can differentially influence research study results and clinical prognosis. Future longitudinal work in larger samples is needed, but Hb obtained over the lifetime appears to provide a more precise picture of patients' cognitive developmental trajectory than a single contemporaneous Hb value alone. Figure 1 Figure 1. Disclosures Kirkham: Bluebird Bio: Honoraria; Novartis: Honoraria; Global Blood Therapeutics: Consultancy. Howard: Imara: Consultancy, Honoraria; Global Blood Therapeutics: Consultancy; Novartis: Consultancy, Honoraria; Resonance Health: Honoraria; Novo Nordisk: Consultancy; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Consultancy; Bluebird Bio: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 14 ( 2023-7-25)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-7-25)
    Abstract: Compared to typically developing children and young adults (CYA-TD), those living with Sickle Cell Disease (CYA-SCD) experience more cognitive difficulties, particularly with executive function. Few studies have examined the relative importance of silent cerebral infarction (SCI), haemoglobin and arterial oxygen content on age-related cognitive changes using cross-sectional or longitudinal (developmental trajectory) data. This study presents cohort data from a single timepoint to inform studies with multiple timepoints. Methods We compared cross-sectional raw and scaled scores as age-related changes in cognition (trajectories) in CYA-SCD and age-and ethnicity-matched CYA-TD. We also compared cross-sectional age-related changes in cognition (trajectories) in CYA-SCD with and without SCI to CYA-TD. General cognitive abilities were assessed using Wechsler Intelligence Scales, including the Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) underpinning IQ. Executive function was evaluated using the Delis-Kaplan Executive Function System (D-KEFS) Tower subtest and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. SCI were identified from contemporaneous 3 T MRI; participants with overt stroke were excluded. Recent haemoglobin was available and oxygen saturation (SpO 2 ) was measured on the day of the MRI. Results Data were available for 120 CYA-SCD [62 male; age = 16.78 ± 4.79 years; 42 (35%) with SCI] and 53 CYA-TD (23 male; age = 17.36 ± 5.16). Compared with CYA-TD, CYA-SCD experienced a delayed onset in VCI and slower rate of development for BRIEF Global Executive Composite, Metacognition Index (MI), and Behaviour Regulation Index. The rate of executive function development for the BRIEF MI differed significantly between CYA-TD and CYA-SCD, with those with SCI showing a 26% delay compared with CYA-TD. For CYA-SCD with SCI, arterial oxygen content explained 22% of the variance in VCI and 37% in PRI, while haemoglobin explained 29% of the variance in PRI. Conclusion Age-related cognitive trajectories of CYA-SCD may not be impaired but may progress more slowly. Longitudinal studies are required, using tests unaffected by practice. In addition to initiation of medical treatment, including measures to improve arterial oxygen content, early cognitive intervention, educational support, and delivery of extracurricular activities could support cognitive development for CYA-SCD.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 9
    In: Healthcare, MDPI AG, Vol. 10, No. 4 ( 2022-04-01), p. 666-
    Abstract: Caregivers of children with autism spectrum disorder (ASD) experience poorer sleep, but studies have not yet used objective measures to investigate how child and caregiver sleep affect each other. In this study, 29 mothers and their child with ASD aged between 6 and 16 years were recruited. Questionnaires measuring child autism, maternal depression, and maternal and child sleep quality were administered. Cortisol salivary samples were also obtained from the mothers over the course of a day. Results revealed that maternal depression is significantly correlated with their subjective sleep quality, sleep latency and daytime dysfunction. Child sleep quality was also found to be significantly correlated with ASD severity. In terms of maternal cortisol profiles, a significant number of mothers showed a flattened diurnal cortisol expression, and children of mothers with a flattened cortisol profile had significantly more sleep problems. Overall, results suggest that maternal and child sleep are affected by the child’s disability but also are mutually related. Future studies may consider employing measures such as actigraphy or somnography to quantify sleep quality and establish causal pathways between sleep, cortisol expression and caregiver and child outcomes. The present study has clinical implications in examining family sleep when considering treatment for ASD.
    Type of Medium: Online Resource
    ISSN: 2227-9032
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2721009-1
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  • 10
    In: British Journal of Haematology, Wiley, Vol. 186, No. 2 ( 2019-07), p. 360-363
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1475751-5
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